DESCRIPTION (Applicant's abstract): Aerobic exercise capacity is a phenotype of fundamental biological and clinical importance. Our long-term goal is to develop genetic models of aerobic exercise capacity in rats that can be used to identify genes responsible for differences between low and high capacity. To achieve this goal we started divergent selective breeding for aerobic treadmill running capacity in a founder population of 192 N/Nih rats. Thirteen mating pairs that demonstrated substantial breeding values were selected from the founder population at the low and high extremes of aerobic capacity. Three generations of selective breeding produced a 117 percent difference in performance between the low and high selected lines for aerobic running capacity. The Specific Aims of this work are to: 1. Continue the selective breeding for aerobic endurance capacity until the response to selection for this trait is diminished in the low and high lines. The selection plateau will be operationally defined as when the response to selection is not significantly different for three successive generations. 2. Create contrasting inbred lines of low and high aerobic performance rats. To accomplish this, 13 families from the low and high selected lines will be strictly brother-sister (full-sib) mated for 20 or more generations. Selection for best aerobic performers will be continued throughout the inbreeding. 3. Continue selective breeding of the divergent lines created in specific aim 1 for 20 or more generations past the apparent plateau. Selective breeding will be continued past the plateau for two reasons: a) to assure that a selection limit has been reached, and b) to serve as a source for originating additional inbred families. By the year 2000 most of the transcribed regions of the human genome will have been sequenced. Although this represents a major achievement, the function of only a small part of the genome will be known. The next step will be the use of genetic models to connect genes with function. Identification-of genes responsible for the differences between low and high aerobic exercise capacity would form a broader base for understanding the genetic origins of health, and lead to new paths for the prevention and treatment of disease.